Copanlisib in Combination With Rituximab and CHOP Chemotherapy in Patients With Previously Untreated DLBCL

Exclusion Criteria

• •Patients who meet any of the following criteria at the time of screening will be excluded.
• •1. Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
• •2. Previous (within 28 days or less than 5 half-lives of the drug before start of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s).
• •3. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent persons (e.g. employee or student of the investigational site).
• •Excluded medical conditions:
• •4. Type I or II diabetes mellitus with HbA1c \> 8.5% at screening or fasting plasma glucose \> 160 mg/dL at screening
• •5. History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
• •6. Known lymphoma involvement of the central nervous system
• •7. Human immunodeficiency virus (HIV) infection
• •8. Hepatitis B (HBV) and C (HCV) infection. Patients with serologic markers of HBV immunization due to vaccination (HBsAg negative, Anti-HBc negative and Anti-HBs positive) will be eligible
• •9. CMV-PCR positive at baseline
• •10. Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated:
• •1. Cervical carcinoma in situ
• •2. Non-melanoma skin cancer
• •3. Superficial bladder cancer (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\])
• •4. Localized prostate cancer
• •11. Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication
• •12. Patients with seizure disorder requiring medication
• •13. Proteinuria of ≥ CTCAE Grade 3 as assessed by a 24h protein quantification or estimated by urine protein: creatinine ratio \> 3.5 on a random urine sample
• •14. Concurrent diagnosis of pheochromocytoma
• •15. Congestive heart failure \> New York Heart Association (NYHA) class 2
• •16. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
• •17. Myocardial infarction less than 6 months before start of test drug
• •18. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
• •19. Non-healing wound, ulcer, or bone fracture
• •20. Active, clinically serious infections \> CTCAE Grade 2
• •21. Uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management)
• •22. Known history of drug induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
• •23. Ongoing inflammatory bowel disease
• •24. History of, or current autoimmune disease
• •25. Prior treatment with PI3K inhibitors
• •26. Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
• •27. Patient is pregnant (β-HCG positive) or breast-feeding
• •28. Known hypersensitivity to copanlisib or to any of the excipients of rituximab, cyclophosphamide, doxorubicine, vincristine, and/or prednisone